DESCRIPTION: (Applicant's Description) A hallmark of our laboratory has been the development of quantitative techniques to gain insight into the physiological processes which limit the effective use of therapeutic agents. The primary scientific focus of this core involves three such fields related by their bioengineering emphasis: mathematical modeling, intravital microscopy, and image analysis. Two other important functions of this core are: maintenance of a variety of computer systems; and biostatistical guidance in experimental design and interpretation and in parameter estimation. Mathematical modeling will be used to help understand transport barriers on a number of length scales and for a variety of therapeutic agents. Whole body, organ level, microscopic, and in vitro models have been developed and used successfully in the past by the lab. In the proposed PPG this aspect of the bioengineering core will be essential in interpreting data in all four projects, e.g. deconvolution of green fluorescence protein signals to quantify gene expression, analyzing data for vascular permeability, interstitial flow and solute transport, and cell trafficking and biodistribution studies. Each project relies on microscopy to quantify microenvironment, gene expression, physiological and biophysical parameters. The bioengineering core will therefore acquire and maintain microscopes, other optical equipment, and related electronic and photographic equipment for recording and analyzing images. The core will also develop new quantitative imaging methods (e.g. fluorescence correlation spectroscopy, continuing the tradition established over the past decade. Core leaders will instruct and assist researchers in the use of microscopy techniques and image analysis software. Image analysis requires the collection, manipulation, analysis, and visualization of complex visual data obtained in all projects. Since this involves considerable and detailed knowledge of software and hardware systems, this important need is best served with a core facility. Likewise, the maintenance of computer hardware, software and networks, programming, and interfacing is best performed with a knowledgeable computer systems manager. Finally, the quantitative aspects of our research methods require close involvement with a biostatistician in all phases of the research: experimental design (protocols and animal calculations), analysis of experimental data, and careful estimation of model parameters with nonlinear regression techniques. The four research projects in this PPG could not be carried out if the services of the bioengineering core component were not available.